I just added a Time Out FAQ item on the differences between the direct and Mac App Store editions of Time Out, and thought it'd make a good blog post.
The direct edition (available from this site) and the Mac App Store edition are very similar, but there are a few minor differences:
That's about it. None of the differences are all that significant, so you are welcome to use whichever edition you prefer. Downloading and updating are about as easy for each, and purchasing is similar, it just depends on whether you want to buy with your credit card or PayPal account, or your Apple ID. Of course, purchasing is optional; you can use it for free if you don't want to become a supporter.